Necroptosis is a form of regulated cell death that is linked to various human diseases. Distinct membrane-related, thus lipid-dependent, alterations take place during necroptosis. However, little is known about the roles of specific lipids in this process. We used an untargeted LC-MS-based approach to reveal that distinct lipid species are regulated at the molecular level during necroptosis. We found that ceramides and very long chain fatty acids accumulate during this process. Intrigued by the specificity of very long chain fatty acid accumulation, we focused on characterizing their involvement during necroptosis. Biochemical characterizations suggested that activated fatty acid biosynthesis and elongation could be responsible for these accumulations. We further showed that inhibition of fatty acid biosynthesis and depletion of very long chain fatty acids prevented loss of plasma membrane integrity and cell death, strongly suggesting that very long chain fatty acids are functionally involved in necroptosis.

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超长链脂肪酸在功能上参与坏死病

坏死病是一种与多种人类疾病有关的受调节的细胞死亡形式。坏死病发生时发生与膜相关的，因此与脂质相关的明显改变。然而，关于特定脂质在该过程中的作用知之甚少。我们使用了一种无针对性的基于LC-MS的方法来揭示坏死性坏死在分子水平上受到调节。我们发现神经酰胺和很长链的脂肪酸在此过程中积累。极长链脂肪酸积累的特殊性引起了我们的兴趣，我们专注于表征其在尸体坏死中的参与。生化特征表明，活化脂肪酸的生物合成和伸长可能是这些积累的原因。